Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor (NCT01207492), a na phase 2 study. The primary outcome is Percentage of Participants With Progression Free Survival.

2. Clinical Question

In practical statistical terms, this is a question about the observed outcome in one treated group, not about the difference between nilotinib and another treatment. The registry’s background describes the study as testing whether nilotinib could stop PVNS growth or improve symptoms, but the registered primary endpoint focuses on progression-free survival at a specified time. The listed secondary outcomes are overall tumor response rate and clinical benefit rate. Their numerical results are not reported in the registry record. The record also does not give enough detail to determine which participants contributed to each endpoint or how incomplete follow-up was handled.

3. Trial Design

This was a multicenter, single-agent phase II study of nilotinib in participants with relapsed or metastatic PVNS, tenosynovial giant cell tumor, or diffuse-type giant cell tumor. The registry lists a total enrollment of 17 and identifies the study as completed. The recorded start is 2010-09, and the primary completion is 2014-04. The sponsor is listed as Andrew J. Wagner, MD, PhD.

The design is single group, with no masking and allocation recorded as not applicable. There is no randomized comparison group. All participants were assigned to the nilotinib arm as described in the record; therefore, the design can describe outcomes among participants treated in the study, but it cannot directly compare those outcomes with outcomes under a concurrent control condition. Differences between the study participants’ outcomes and any external benchmark would not, by themselves, establish a treatment effect.

The intervention is classified as a drug, and the arm description states that nilotinib was taken continuously. The primary endpoint is the percentage of participants with progression-free survival at 6 months. The listed secondary outcomes are overall tumor response rate and clinical benefit rate. Details of the assessment schedule, follow-up duration beyond the primary time point, and criteria for the secondary outcomes are not reported in the registry record.

The registry record does not report a sample-size justification or the statistical plan used to guide the trial’s design. A planning illustration based on an observed effect is not the same as a prespecified enrollment target or a trial’s design rationale. In particular, planning assumptions involving equal allocation between two arms do not describe this single-group study. The record also does not report interim analyses, a control-arm plan, or a masking procedure beyond stating that masking was none.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Progression Free Survival, measured over 6 months.

The primary endpoint is the percentage of participants with progression-free survival at 6 months. It is intended to describe the proportion of the study group who remain free of the defined progression event at that time point. The registry record defines progression using RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions.

A fixed-time progression-free survival endpoint can be useful because it expresses disease status at a clinically interpretable follow-up point rather than only reporting the number of events over an unspecified period. A confidence interval communicates uncertainty around an estimated percentage: narrower intervals indicate greater precision, while wider intervals indicate less precision. These are general statistical interpretations, not additional findings about this study.

The registry identifies the dispersion measure as a 95% confidence interval, but does not report the endpoint estimate or interval limits. It also does not report details needed to reconstruct the analysis, such as how participants with incomplete follow-up were treated, the analysis population, or the method used to estimate the percentage. The endpoint description lists progression criteria; whether any additional event definition was included is not reported in the registry record. Without the numerical estimate and its uncertainty, the endpoint’s observed magnitude and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is expressed as a percentage at a fixed time point. In general, a percentage for a binary outcome describes the share of an analyzed group classified as having the outcome. Its interpretation depends on how the outcome is defined, which participants are included, and how missing observations are handled. The registry specifies the endpoint and its time point, but does not report the estimated percentage or the analysis population. It is therefore not possible to verify the result or determine exactly which participants contributed to it.

The progression definition uses RECIST v1.1 criteria. The record identifies three progression events: a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. These criteria give a structured basis for classifying tumor progression. The record does not report further operational details about assessment timing, confirmation of progression, or how assessments that could not be evaluated were classified.

The registry lists a 95% confidence interval for the primary endpoint. In general, a confidence interval gives a range of values compatible with the observed data under the method’s assumptions. It is not a guarantee that the true value lies in the interval, and it does not by itself correct for bias, missing data, or an unsuitable study design. The interval’s width helps describe precision, while the point estimate describes the central estimate. Neither the point estimate nor the interval bounds are reported in the registry record, so neither magnitude nor precision can be evaluated.

The single-group design determines what comparisons are available. In general, an estimate from a treated group describes that group’s observed outcomes. A treatment contrast requires a comparison condition; without one, it is not possible to estimate the difference between outcomes under the study intervention and a concurrent alternative. The record identifies no randomized allocation and no comparator arm. Thus, any interpretation of the primary endpoint would be descriptive for the enrolled group, rather than a randomized estimate of comparative effect.

Planning illustrations based on observed effects answer a different question from trial results. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is total events; other illustrations use participants per arm. These are planning conventions, not evidence that the study used a two-arm design. This trial is registered as single group, and the registry record does not report its own sample-size justification. Such illustrations are not observed power and should not be read as the number of participants actually analyzed.

In general, power is a design concept: it describes the probability that a statistical procedure will detect a specified effect under stated assumptions. A retrospective calculation using an observed effect is not a measure of how likely the completed study was to detect that effect before it began. The record does not report a prespecified effect size, a planned power target, or a sample-size calculation for this trial. The sample-size assumptions described for planning illustrations do not fill those gaps.

The record identifies three outcome measures and names overall tumor response rate and clinical benefit rate as secondary outcomes. Statistical interpretation across multiple outcomes can be affected by multiplicity: when several questions are examined, the chance of at least one apparently notable result may increase if each is assessed independently. General approaches include prespecifying a primary question, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report a multiplicity procedure, and it does not provide analysis results or test details from which one could infer the approach used.

Over-dispersion is a general issue for count outcomes when variability exceeds what a simple model assumes. It is not a method reported for this primary endpoint, which is described as a percentage of participants with an event at a fixed time. More broadly, the statistical method used to calculate the endpoint estimate and confidence interval is not reported in the registry record. No particular estimation method should be attributed to this trial without that information.

For a single-group study, the most informative statistical reporting would include the analyzed population, the endpoint estimate, its confidence interval, the number of participants with available assessment, and how incomplete follow-up was handled. These details allow readers to understand both the data contributing to the estimate and the uncertainty around it. The registry record does not report these analysis details or the primary endpoint result. Consequently, the intended statistical question can be described, but the underlying calculation cannot be independently evaluated from the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Nilotinib")
n      <- c(17)
events <- c(14)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Nilotinib  17  14  82.4  56.6  96.2  59.0  93.8  58.6  93.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, with overall tumor response rate and clinical benefit rate named as secondary outcomes. The primary endpoint is progression-free survival at 6 months. The record does not report a multiplicity strategy, such as adjustment for evaluating several outcomes, a hierarchy among secondary questions, or a distinction between confirmatory and exploratory analyses. Without that information and without numerical results, it is not possible to assess how multiple outcome testing may have influenced interpretation.

The registry does not report how missing outcome data were handled. It does not specify whether participants without an assessment at the relevant time point were excluded, counted in a particular category, or handled using a statistical method. The endpoint’s analysis population is also not reported. Enrollment of 17 does not establish how many participants contributed to the primary endpoint, and the record does not provide an analyzed denominator.

The record lists no analyses. This absence should not be interpreted as evidence that no analyses were performed; it means that the registry record does not report analysis results or methods. Details such as a prespecified analysis plan, interim analyses, sensitivity analyses, and the handling of participants who discontinued or had incomplete follow-up are not reported in the registry record.

These omissions limit reproducibility and make it difficult to distinguish uncertainty arising from the outcome data from uncertainty arising from analysis choices. They also prevent assessment of whether the primary endpoint was analyzed as planned. No assumptions about missingness or analysis populations can be made from the registry record alone.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fatigue (11.8%), electrocardiogram qt corrected interval prolonged (5.9%), hypophosphatemia (5.9%), rash maculo-papular (5.9%).

The registry record lists 17 participants at risk for serious adverse events and reports 2 affected. For other adverse events, it lists 17 at risk and 17 affected. These are the registry’s overall figures for the nilotinib group; they do not, by themselves, describe severity, duration, relatedness to treatment, or the number of distinct events experienced by each participant.

The serious adverse event terms listed are fatigue at 11.8%, electrocardiogram QT corrected interval prolonged at 5.9%, hypophosphatemia at 5.9%, and rash maculo-papular at 5.9%. These percentages are reported as listed; the record does not provide further detail about event counts by term, timing, clinical course, or attribution. A term appearing in the list should not be read as a complete account of all safety events.

Deaths are not reported in the registry record. The adverse-event figures are descriptive and should be interpreted in light of the single-group design and the enrolled group size. They do not establish comparative safety relative to another treatment, and the registry record does not provide a control group for such a comparison.

13. What the Result Does, and Does Not, Mean

The registry record documents a completed, single-group phase II study of nilotinib in participants with relapsed or metastatic PVNS and related giant cell tumor diagnoses. It identifies a primary question about the percentage with progression-free survival at 6 months and describes progression criteria using RECIST v1.1. It also lists overall tumor response rate and clinical benefit rate as secondary outcomes. These details establish what the study was intended to assess.

The numerical primary endpoint result and its 95% confidence interval are not reported in the registry record. The secondary outcome values and their analysis details are not reported either. Therefore, the registry record cannot establish the observed frequency of progression-free survival, the precision of that estimate, or the pattern of results across outcomes. Completion status is not a substitute for results.

The single-group design also limits what could be concluded even if an outcome estimate were available. A descriptive outcome in participants receiving nilotinib is not the same as a comparison showing how outcomes differ under another treatment. In general, an uncontrolled result can be influenced by the participants’ characteristics, the natural course of disease, outcome assessment, and follow-up. The study design does not separate those factors from the treatment-associated observation.

The reported safety figures describe adverse events recorded in the nilotinib group, including the count of participants affected by serious adverse events and selected serious adverse event terms. They do not provide a randomized safety comparison. The record also does not report deaths or further details needed to understand event attribution and course.

The appropriate reading is therefore narrow: the registry records the design, planned endpoint, progression definition, and some adverse-event figures, but does not report the efficacy endpoint results or confidence interval. No conclusion about treatment benefit or lack of benefit follows from that absence. The missing numerical results and analysis details prevent a full statistical assessment of the intended primary question.

14. Why This Trial Matters Statistically

This trial is statistically notable as a single-group phase II study with a fixed-time primary endpoint. That design focuses on estimating an outcome within a treated group rather than comparing outcomes across randomized treatment arms. Recognizing this distinction is essential: a single-group estimate may describe what happened among enrolled participants, but it does not directly estimate a treatment contrast.

The endpoint is stated as a percentage with progression-free survival at 6 months, and the registry identifies a 95% confidence interval as its dispersion measure. That pairing reflects two useful parts of statistical reporting: an estimate of the outcome and an indication of its precision. Here, however, the numerical estimate and interval are not reported in the registry record. The record therefore names the intended summary but does not provide the quantities needed to interpret it.

The study also illustrates why enrollment, analysis populations, and endpoint results are distinct. The record reports 17 enrolled participants, but does not state how many contributed to the primary endpoint analysis or how incomplete observations were handled. Enrollment alone does not reveal the effective information available for an endpoint estimate, and it cannot establish the estimate’s precision without the results and analysis details.

Finally, the record includes multiple outcomes, including overall tumor response rate and clinical benefit rate, without reporting a multiplicity approach or the corresponding results. This makes it especially important not to infer a coherent pattern of efficacy from the outcome list alone. Statistically, the record is informative about the intended question and design limitations, while the absent results prevent assessment of the observed effect and its uncertainty.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important limitation for interpreting the registered efficacy question is that the primary endpoint result and its 95% confidence interval are not reported in the registry record. The listed secondary outcomes also lack numerical results. The study’s completed status does not resolve this reporting gap.

The single-group design provides no concurrent comparator, and allocation is recorded as not applicable. As a result, the study cannot support a like-for-like randomized contrast. Any observed outcome in this group would remain descriptive, with no direct way to separate treatment-associated observations from other influences on disease course or assessment.

The total enrollment was 17, but the analyzed population and endpoint denominator are not reported. The registry record does not state how missing assessments, discontinuation, or incomplete follow-up were handled. These omissions limit assessment of both the estimate and the possibility that the analyzed participants differed from those enrolled.

Further details of the statistical plan are not reported, including the method used to calculate the endpoint estimate and confidence interval, any multiplicity approach, and whether interim or sensitivity analyses were conducted. The record also does not report definitions and analysis procedures for the secondary outcomes beyond their names. The progression criteria are stated, but additional assessment procedures are not reported.

For safety, the record gives aggregate affected counts and selected serious adverse event terms, but does not report deaths or further event-level information such as timing, duration, attribution, or clinical course. These limitations restrict the scope of what can be inferred from the registry record and prevent a complete statistical or clinical characterization of the study results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor — NCT01207492.
• Registry record last updated 2026-02-20; status last verified 2026-02.
• Results first posted 2015-06-25.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01207492 is a completed, multicenter, single-agent phase II study of nilotinib in relapsed or metastatic PVNS and related giant cell tumor conditions. The registry reports 17 enrolled participants, no masking, no randomized allocation, and a single-group design. The recorded study start is 2010-09, and primary completion is 2014-04.

The primary endpoint was the percentage of participants with progression-free survival at 6 months, with progression defined using RECIST v1.1 criteria. Overall tumor response rate and clinical benefit rate are listed as secondary outcomes. The primary endpoint estimate, its 95% confidence interval, and secondary outcome results are not reported in the registry record.

The record reports 2 participants affected by serious adverse events among 17 at risk, and 17 affected by other adverse events among 17 at risk. It lists selected serious adverse event terms and percentages. A comparator group, analysis population, missing-data approach, and detailed statistical analysis plan are not reported in the registry record.